Page last updated: 2024-10-24

adenylate cyclase inhibiting G protein-coupled glutamate receptor activity

Definition

Target type: molecularfunction

Combining with glutamate and transmitting the signal across the membrane by activating the alpha-subunit of an associated heterotrimeric G-protein complex to inhibit downstream adenylate cyclase activity. [GOC:bf, GOC:dph]

Adenylate cyclase inhibiting G protein-coupled glutamate receptors are a class of metabotropic glutamate receptors (mGluRs) that are characterized by their ability to inhibit the activity of adenylate cyclase, an enzyme that produces cyclic AMP (cAMP). These receptors are coupled to inhibitory G proteins, specifically Gi/o proteins, which upon activation, inhibit adenylate cyclase and consequently reduce intracellular cAMP levels. The mechanism of action involves the following steps:

1. **Ligand Binding:** Glutamate, the primary excitatory neurotransmitter in the brain, binds to the extracellular domain of the receptor.
2. **Conformational Change:** Glutamate binding triggers a conformational change in the receptor protein, activating its intracellular domain.
3. **G Protein Coupling:** The activated receptor interacts with and activates a G protein, specifically a Gi/o protein.
4. **Adenylate Cyclase Inhibition:** The activated Gi/o protein binds to and inhibits adenylate cyclase, reducing its activity.
5. **cAMP Reduction:** Consequently, the intracellular concentration of cAMP decreases.

The reduction in cAMP levels has various downstream effects, depending on the specific cell type and signaling pathways involved. In general, the inhibition of adenylate cyclase can lead to:

* **Reduced protein kinase A (PKA) activity:** cAMP is a key activator of PKA, so reduced cAMP levels result in decreased PKA activity.
* **Modulation of ion channel activity:** cAMP influences the activity of certain ion channels, and its reduction can alter their function.
* **Changes in gene expression:** cAMP can regulate gene transcription, and its decrease can affect the expression of specific genes.

The precise physiological roles of adenylate cyclase inhibiting G protein-coupled glutamate receptors vary depending on their specific subtype and location in the brain. However, they are known to play important roles in processes such as:

* **Synaptic plasticity:** They can modulate synaptic transmission and contribute to long-term potentiation (LTP) and long-term depression (LTD).
* **Neuroprotection:** They may protect neurons from excitotoxicity and other forms of damage.
* **Anxiety and depression:** They are implicated in the regulation of mood and emotional states.

In summary, adenylate cyclase inhibiting G protein-coupled glutamate receptors are important modulators of neuronal signaling, contributing to various physiological processes in the brain.'
"

Proteins (5)

ProteinDefinitionTaxonomy
Metabotropic glutamate receptor 6A metabotropic glutamate receptor 6 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O15303]Homo sapiens (human)
Metabotropic glutamate receptor 5A metabotropic glutamate receptor 5 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P41594]Homo sapiens (human)
Metabotropic glutamate receptor 4A metabotropic glutamate receptor 4 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q14833]Homo sapiens (human)
Metabotropic glutamate receptor 1A metabotropic glutamate receptor 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q13255]Homo sapiens (human)
Glutamate receptor ionotropic, kainate 3A glutamate receptor ionotropic, kainate 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q13003]Homo sapiens (human)

Compounds (89)

CompoundDefinitionClassesRoles
benzoic acidaromatic carboxylic acid : Any carboxylic acid in which the carboxy group is directly bonded to an aromatic ring.

benzoic acid : A compound comprising a benzene ring core carrying a carboxylic acid substituent.

Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to GLYCINE in the liver and excreted as hippuric acid.
benzoic acidsalgal metabolite;
antimicrobial food preservative;
drug allergen;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
EC 3.1.1.3 (triacylglycerol lipase) inhibitor;
human xenobiotic metabolite;
plant metabolite
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acidalpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid: An IBOTENIC ACID homolog and glutamate agonist. The compound is the defining agonist for the AMPA subtype of glutamate receptors (RECEPTORS, AMPA). It has been used as a radionuclide imaging agent but is more commonly used as an experimental tool in cell biological studies.non-proteinogenic alpha-amino acid
alpha-methyl-4-carboxyphenylglycine
ibotenic acidIbotenic Acid: A neurotoxic isoxazole (similar to KAINIC ACID and MUSCIMOL) found in AMANITA mushrooms. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist.non-proteinogenic alpha-amino acidneurotoxin
4-carboxy-3-hydroxyphenylglycine4-carboxy-3-hydroxyphenylglycine: weak agonist at metabotropic glutamate receptors; occludes the action of 1-aminocyclopentyl-1,3-dicarboxylate in hippocampushydroxybenzoic acid
1-aminoindan-1,5-dicarboxylic acid1-aminoindan-1,5-dicarboxylic acid: structure given in first source
2-amino-4-phosphonobutyric acid2-amino-4-phosphonobutyric acid: glutamate antagonist in locust muscle; structure; do not confuse with L-AP4, which is the propionic acid version
miconazole1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]imidazole : A member of the class of imidazoles that is 1-(2,4-dichlorophenyl)-2-(imidazol-1-yl)ethanol in which the hydroxyl hydrogen is replaced by a 2,4-dichlorobenzyl group.

miconazole : A racemate composed of equimolar amounts of (R)- and (S)-miconazole. Used (as its nitrate salt) to treat skin infections such as athlete's foot, jock itch, ringworm and other fungal skin infections. It inhibits the synthesis of ergosterol, a critical component of fungal cell membranes.

Miconazole: An imidazole antifungal agent that is used topically and by intravenous infusion.
dichlorobenzene;
ether;
imidazoles
4-carboxyphenylglycine4-carboxyphenylglycine: RN given for (+-)-isomer; RN for cpd without isomeric designation not available 3/93; glutamate receptor antagonistalpha-amino acid
aspartic acidaspartic acid : An alpha-amino acid that consists of succinic acid bearing a single alpha-amino substituent

Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.

L-aspartic acid : The L-enantiomer of aspartic acid.
aspartate family amino acid;
aspartic acid;
L-alpha-amino acid;
proteinogenic amino acid
Escherichia coli metabolite;
mouse metabolite;
neurotransmitter
kainic acidKainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.dicarboxylic acid;
L-proline derivative;
non-proteinogenic L-alpha-amino acid;
pyrrolidinecarboxylic acid
antinematodal drug;
excitatory amino acid agonist
d-glutamateD-alpha-amino acid;
glutamic acid
Escherichia coli metabolite;
mouse metabolite
glutamic acidglutamic acid : An alpha-amino acid that is glutaric acid bearing a single amino substituent at position 2.

Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.
glutamic acid;
glutamine family amino acid;
L-alpha-amino acid;
proteinogenic amino acid
Escherichia coli metabolite;
ferroptosis inducer;
micronutrient;
mouse metabolite;
neurotransmitter;
nutraceutical
quisqualic acidQuisqualic Acid: An agonist at two subsets of excitatory amino acid receptors, ionotropic receptors that directly control membrane channels and metabotropic receptors that indirectly mediate calcium mobilization from intracellular stores. The compound is obtained from the seeds and fruit of Quisqualis chinensis.non-proteinogenic alpha-amino acid
quinpirolequinpirole : A pyrazoloquinoline that is (4aR,8aR)-4,4a,5,6,7,8,8a,9-octahydro-1H-pyrazolo[3,4-g]quinoline substituted by a propyl group at position 5. It acts as a dopamine agonist.

Quinpirole: A dopamine D2/D3 receptor agonist.
pyrazoloquinolinedopamine agonist
plasmenylserineO-phospho-L-serine : The L-enantiomer of O-phosphoserine.

O-phosphoserine : A serine derivative that is serine substituted at the oxygen atom by a phosphono group.

plasmenylserine: RN given refers to (L)-isomer
O-phosphoserineEC 1.4.7.1 [glutamate synthase (ferredoxin)] inhibitor;
EC 2.5.1.49 (O-acetylhomoserine aminocarboxypropyltransferase) inhibitor;
EC 4.3.1.10 (serine-sulfate ammonia-lyase) inhibitor;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
1-amino-1,3-dicarboxycyclopentane, (trans)-isomer
d-aspartic acidaspartic acid;
D-alpha-amino acid
mouse metabolite
L-2-aminoadipic acidL-2-aminoadipic acid : The L-enantiomer of 2-aminoadipic acid.2-aminoadipic acidEscherichia coli metabolite;
human metabolite
sym 2081
alpha-aminopimelic acid2-aminopimelic acid : An amino dicarboxylic acid that is heptanedioic acid in which a hydrogen at position 2 is replaced by an amino group. It is a component of the cell wall peptidoglycan of bacteria.

alpha-aminopimelic acid: antagonizes glutamate-induced inhibitions of Helix neurones
amino dicarboxylic acid;
non-proteinogenic alpha-amino acid
bacterial metabolite
1-amino-1,3-dicarboxycyclopentane1-amino-1,3-dicarboxycyclopentane: RN given refers to (cis)-isomer
1-amino-3-(phosphonomethylene)cyclobutane-1-carboxylic acid1-amino-3-(phosphonomethylene)cyclobutane-1-carboxylic acid: potently inhibits evoked field potentials in the rat lateral perforant path; structure given in first source
ly 293558tezampanel: structure given in first source; an AMPA receptor antagonist
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
philanthotoxin 343philanthotoxin 343: structure given in first source (see article's footnote); identical to philanthotoxin 433 except that the number of methylene groups between the respective amine moieties is 3,4,3 instead of 4,3,3N-acyl-amino acid
alpha-amino-3-(hydroxy)-5-methyl-4-isoxazoleacetic acidalpha-amino-3-(hydroxy)-5-methyl-4-isoxazoleacetic acid: RN given refers to cpd without isomeric designation; structure given in first source
homocysteic acidhomocysteic acid : A non-proteinogenic alpha-amino acid that is homocysteine in which the thiol group has benn oxidised to the corresponding sulfonic acid.

homocysteic acid: promotes growth in hypophysectomized rats; RN given refers to parent cpd

L-homocysteic acid : A homocysteic acid with L-configuration.
homocysteic acidNMDA receptor agonist
2-amino-4-phosphonobutyric acid(2S)-2-amino-4-phosphonobutanoic acid : A non-proteinogenc L-alpha-amino acid that is L-alpha-aminobutyric acid in which one of the hydrogens of the terminal methyl group has been replaced by a dihydroxy(oxido)-lambda(5)-phosphanyl group. It is a potent and selective agonist for the group III metabotropic glutamate receptors (mGluR4/6/7/8).non-proteinogenic L-alpha-amino acid;
phosphonic acids
metabotropic glutamate receptor agonist
eglumetadeglumetad: LY-354740 is the active isomer, LY-366563 is the inactive isomer, and LY 314582 is the racemate; structure given in first sourceL-alpha-amino acid
3,5-dihydroxyphenylglycine(S)-3,5-dihydroxyphenylglycine : A glycine derivative that is L-alpha-phenylglycine substituted at positions 3 and 5 on the phenyl ring by hydroxy groups.amino acid zwitterion;
non-proteinogenic L-alpha-amino acid;
resorcinols
alpha-methyl-4-carboxyphenylglycine(S)-alpha-methyl-4-carboxyphenylglycine : A non-proteinogenic alpha-amino acid that is alanine in which the alpha-hydrogen is replaced by a 4-carboxyphenyl group (the S-enantiomer). It is a non-selective group I/group II metabotropic glutamate receptor (mGluR) antagonist.

alpha-methyl-4-carboxyphenylglycine: glutamate receptor antagonist
non-proteinogenic alpha-amino acidmetabotropic glutamate receptor antagonist
n-(3-chlorophenyl)picolinamideN-(3-chlorophenyl)picolinamide: a metabotropic glutamate receptor 4 (mGlu4) positive allosteric modulator; structure in first source
vu 0155041VU 0155041: an mGluR4 agonist
9-(dimethylamino)-3-(4-methoxyphenyl)-4-pyrido[1,2]thieno[3,4-d]pyrimidinoneorganic heterobicyclic compound;
organonitrogen heterocyclic compound;
organosulfur heterocyclic compound
4-bromohomoibotenic acid, (rs)-isomer
6-methyl-2-(phenylethynyl)pyridine2-methyl-6-(phenylethynyl)pyridine : A methylpyridine that coinsists of 2-methylp[yridine bearing an additional phenylethynyl group at position 6. Potent and highly selective non-competitive antagonist at the mGlu5 receptor subtype (IC50 = 36 nM) and a positive allosteric modulator at mGlu4 receptors. Centrally active following systemic administration in vivo. Reverses mechanical hyperalgesia in the inflamed rat hind paw.

6-methyl-2-(phenylethynyl)pyridine: an mGlu5 antagonist
acetylenic compound;
methylpyridines
anxiolytic drug;
metabotropic glutamate receptor antagonist
4-methylglutamic acid, threo-(l)-isomer
2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline: structure given in first source; neuroprotectant for cerebral ischemia; AMPA receptor antagonistnaphthalenes;
sulfonic acid derivative
2-chloro-5-hydroxyphenylglycine2-chloro-5-hydroxyphenylglycine: activates mGlu(5) receptors; structure in first source
vu0155094VU0155094: a positive allosteric modulator of metabotropic glutamate receptor 7; structure in first source
sib 1757SIB 1757: a selective mGluR5 antagonist; structure in first source
l-2-(carboxypropyl)glycine
2-(2,3-dicarboxycyclopropyl)glycine
2r,4r-4-aminopyrrolidine-2,4-dicarboxylatepyrrolidinedicarboxylic acid
upf 596UPF 596: structure in first source
ly-367385
sib 1893SIB 1893: a selective mGluR5 antagonist; structure in first source
4-carboxy-3-hydroxyphenylglycine
ubp 302
1-amino-1,3-dicarboxycyclopentane, cis-(1s,3s)-isomer
ampa, (r)-isomer
1-aminocyclopentane-1,3,4-tricarboxylic acid1-aminocyclopentane-1,3,4-tricarboxylic acid: metabolic glutamate receptor (mGluR) antagonist; structure in first source
dinitrofluorobenzene3,3'-difluorobenzaldazine: a selective positive allosteric modulator of mGluR5 activity; structure in first source
3-((2-methyl-1,3-thiazol-4-yl)ethynyl)piperidine3-((2-methyl-1,3-thiazol-4-yl)ethynyl)piperidine: an excitatory amino acid antagonist
ly 341495xanthenes
mgs 0028MGS 0028: a group II mGluR agonist; structure in first source
azd9272AZD9272: an mGluR5 antagonist
bay36-7620BAY36-7620: a potent non-competitive mGlu1 receptor antagonist with inverse agonist activity. ; structure in first source
mavoglurantmavoglurant: antagonist of metabotropic glutamate receptor 5
n-(4-chloro-2-((1,3-dioxo-1,3-dihydro-2h-isoindol-2-yl)methyl)phenyl)-2-hydroxybenzamideN-(4-chloro-2-((1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl)phenyl)-2-hydroxybenzamide: a positive allosteric modulator of mGluR5; structure in first source
ly 389795LY 389795: a group II metabotropic glutamate receptor agonist; structure in first source
ly 379268LY 379268 : An organic heterobicyclic compound that is (1R,5S)-2-oxabicyclo[3.1.0]hexane carrying amino, carboxy, and carboxy groups at positions 4R, 4R and 6R, respectively. It is a potent agonist of group II metabotropic glutamate receptors mGluR2 and mGluR3 (EC50 = 2.69 nM and 4.48 nM, respectively) that exhibits antipsychotic-like action in animal models of schizophrenia.

LY 379268: group II metabotropic glutamate receptor agonist; structure in first source
amino dicarboxylic acid;
bridged compound;
organic heterobicyclic compound
antipsychotic agent;
anxiolytic drug;
metabotropic glutamate receptor agonist;
neuroprotective agent
3-(5-pyridin-2-yl-2h-tetrazol-2-yl)benzonitrile3-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile: structure in first source
3-fluoro-5-(5-pyridin-2-yl-2h-tetrazol-2-yl)benzonitrile3-fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile: structure in first source
r 214127R 214127: an mGlu1 receptor ligand; structure in first source
3-cyano-n-(1,3-diphenyl-1h-pyrazol-5-yl)benzamide3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide: affects mGluR5 receptors; structure in first source
jnj16259685organic heterotricyclic compound;
organonitrogen heterocyclic compound;
oxacycle
adx 47273
basimglurant
a 794282
a-841720A-841720: structure in first source
ro 49563712-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine: a metabotropic glutamate receptor 5 antagonist; structure in first source
ubp296UBP296: potent and selective kainate receptor antagonist; structure in first sourcealpha-amino acid
vu0092273VU0092273: mGlu(5) positive allosteric modulator
3,4-dicarboxyphenylglycine
sp 2033-fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile: a radioligand for mGlu5 receptor; structure in first source
vu0361737
6-fluoro-2-(4-(pyridin-2-yl)but-3-yn-1-yl)imidazo(1,2-a)pyridine6-fluoro-2-(4-(pyridin-2-yl)but-3-yn-1-yl)imidazo(1,2-a)pyridine: an mGluR5 antagonist; structure in first source
5-methyl-n-(4-methylpyrimidin-2-yl)-4-(1h-pyrazol-4-yl)thiazol-2-amine5-methyl-N-(4-methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)thiazol-2-amine: an mGlu4 positive modulator; structure in first source
wms 1410
vu0409106VU0409106: a metabotropic glutamate receptor 5 antagonist; structure in first source
n-cyclobutyl-6-((3-fluorophenyl)ethynyl)nicotinamideN-cyclobutyl-6-((3-fluorophenyl)ethynyl)nicotinamide: an mGlu5 agonist; structure in first source
ml289ML289: metabotropic glutamate receptor 3 probe
lsp4-2022LSP4-2022: structure in first source
lsn2463359
vu0422288VU0422288: a positive allosteric modulator of metabotropic glutamate receptor 7; structure in first source
3-chloro-5-(6-(5-fluoropyridin-2-yl)pyrimidin-4-yl)benzonitrile3-chloro-5-(6-(5-fluoropyridin-2-yl)pyrimidin-4-yl)benzonitrile: a metabotropic glutamate receptor 5 antagonist; structure in first source
fenobamfenobam: in USAN fenobam refers to monohydrateureas